Safety and immunogenicity of the candidate tuberculosis vaccine MVA85A in West Africa

Roger H Brookes, Philip C Hill, Patrick K Owiafe, Hannah B Ibanga, David J Jeffries, Simon A Donkor, Helen A Fletcher, Abdulrahman S Hammond, Christian Lienhardt, Richard A Adegbola, Helen McShane, Adrian V S Hill, Roger H Brookes, Philip C Hill, Patrick K Owiafe, Hannah B Ibanga, David J Jeffries, Simon A Donkor, Helen A Fletcher, Abdulrahman S Hammond, Christian Lienhardt, Richard A Adegbola, Helen McShane, Adrian V S Hill

Abstract

Background: Vaccination with a recombinant modified vaccinia Ankara expressing antigen 85A from Mycobacterium tuberculosis, MVA85A, induces high levels of cellular immune responses in UK volunteers. We assessed the safety and immunogenicity of this new vaccine in West African volunteers.

Methods and findings: We vaccinated 21 healthy adult male subjects (11 BCG scar negative and 10 BCG scar positive) with MVA85A after screening for evidence of prior exposure to mycobacteria. We monitored them over six months, observing for clinical, haematological and biochemical adverse events, together with assessment of the vaccine induced cellular immune response using ELISPOT and flow cytometry. MVA85A was well tolerated with no significant adverse events. Mild local and systemic adverse events were consistent with previous UK trials. Marked immunogenicity was found whether individuals had a previous BCG scar or not. There was not enhanced immunogenicity in those with a BCG scar, and induced T cell responses were better maintained in apparently BCG-naïve Gambians than previously studied BCG-naïve UK vaccinees. Although responses were predominantly attributable to CD4+ T cells, we also identified antigen specific CD8+ T cell responses, in subjects who were HLA B-35 and in whom enough blood was available for more detailed immunological analysis.

Conclusions: These data on the safety and immunogenicity of MVA85A in West Africa support its accelerated development as a promising booster vaccine for tuberculosis.

Trial registration: ClinicalTrials.gov NCT00423839.

Conflict of interest statement

Competing Interests: RHB has a patent relating to ex vivo ELISPOT licensed through Oxford University. AH and HM are named inventors on a composition of matter patent for MVA85A filed by the University of Oxford. There are no other conflicts of interest

Figures

Figure 1. Timeline for vaccination and blood…
Figure 1. Timeline for vaccination and blood sampling schedules.
A. BCG scar negative subjects. B. BCG scar positive subjects.
Figure 2. Median Ex-vivo interferon-gamma ELISPOT responses…
Figure 2. Median Ex-vivo interferon-gamma ELISPOT responses to Ag85A protein, PPD-T and Ag85A overlapping peptides after MVA85A vaccination in healthy male volunteers.
A. BCG scar negative vaccines (n = 11); B. BCG scar positive vaccinees (n = 10).
Figure 3. CD8+ and CD4+ T cell…
Figure 3. CD8+ and CD4+ T cell responses. A.
Short term cell lines specific for p23 were generated using PBMC recovered 28 days after vaccination and specificity demonstrated by flow cytometry. Gating on IFN-γ detection, both CD4 and CD8 responses were observed for one subject (volunteer 1) while for the other subject (volunteer 2) an exclusive CD8 response was identified. B. Volunteer 2 also showed CD4 and CD8 activation by CD69 expression after stimulation with pooled Ag85A peptides 28 days after vaccination.

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